This research aims to increase understanding of the pathogenesis of Alzheimer's disease and senile dementia of the Alzheimer type (SDAT) by investigating the composition and characteristics of the neurofibrillary tangles (NFT) and neuritic, or senile, plaques which are central features of the pathology of SDAT. The overall objective is to elucidate changes and disease processes in SDAT and to seek clues to its etiology. Comparison with other conditions associated with NFT and plaques, including normal aging, may indicate whether findings in SDAT are specific or represent responses to possibly diverse stimuli, and may shed light on SDAT. This laboratory has recently demonstrated that NFT in paraffin sections of SDAT brain processed by the peroxidase-antiperoxidase technique are specifically immuno-stained by a rabbit antiserum raised against partially purified normal human brain microtubules. The cross-reacting normal antigen is not known but does not appear to be tubulin. This laboratory also has demonstrated two nucleoside phosphatase histochemical reactivities which appear to be associated with NFT and plaques in Alzheimer's disease. In this project, human autopsy and animal (rabbit, rodent, bovine) tissue will be studied with immunocytochemical and enzyme histochemical light and electron microscope methods. The tangle-reactive rabbit antiserum will be used to compare NFT in various conditions and to examine ultrastructurally the NFT antibody-binding site. The project also aims to use normal human brain microtubule fractions to elicit mouse monoclonal antibodies cross-reactive with NFT. The monoclonal antibodies will be employed for comparative and ultrastructural studies on NFT, but in addition will be used to investigate the normal antigen cross-reactive with NFT. The species and tissue distribution of the normal antigen and its ultrastructural localization will be examined, perhaps it will be identified, and possible age- or SDAT-related antigen changes will be investigated. Other immunocytochemical studies aim to elucidate the origin of plaque amyloid in SDAT. Histochemical experiments will seek to characterize further NFT and plaque nucleoside phosphatase activities.